Hemophilic Joint Bleeding Promotes Vascular Remodeling, Rebleeding Independent of Hemostatic Correction

Share this content:
Hemophilic joint bleeding often leads to aberrant expression of alpha-smoot muscle actin, which can indicate vascular remodeling.
Hemophilic joint bleeding often leads to aberrant expression of alpha-smoot muscle actin, which can indicate vascular remodeling.

In addition to promoting vascular permeability and rebleeding, vascular remodeling due to hemophilic joint bleeding occurs independently of hemostatic correction, according to data published in Haemophilia.

Hemophilic joint bleeding can lead to aberrant, excessive alpha-smooth muscle actin (alpha-SMA) expression. This is indicative of vascular and tissue remodeling which can lead to weaker blood vessels and further bleeding.

The authors of this study attempted to elucidate the effects of hemophilic joint bleeding by inducing joint bleeding in 3 cohorts of mice: factor VIII (FVIII)-deficient mice that received FVIII-treatment, FVIII-deficient mice that received anti-VEGF treatment, and wild-type mice anticoagulated with warfarin and given anti-FVIII-antibody treatment. The authors then measured the resulting vascular and tissue changes, synovial permeability, and rebleeding. Data was also collected from 31 human adults with hemophilic arthopathy regarding bleed status, vascular flow, and plasma markers of collagen turnover.

At 2 weeks, the joint bleeding had triggered marked synovial vascular abnormalities in both cohorts of FVIII-deficient mice, unmitigated by FVIII-treatment. These abnormalities, which were no longer associated with synovial permeability, persisted at 4 weeks only in the mice that were not receiving FVIII-treatment.

Furthermore, FVIII-treatment failed to prevent synovial dysregulation of the vascular basement membrane and extracellular matrix of the mice. The vascular basement membrane was dysregulated in the patients as well, and high collagen metabolite counts were observed during joint bleeding in comparison with baseline and non-bleeding episodes, in spite of clotting factor prophylaxis and treatment.

The mice treated with anti-VEGF did not demonstrate vascular remodeling, permeability, or rebleeding, showing that vascular aberrancy increases the potential for rebleeding.

The authors suggested that vascular remodeling is linked to the lack of continuous FVIII, but remodeling and rebleeding also occur independently of treatment and hemostatic processes. They concluded that vascular tissue remodeling “seems to occur independently of hemostasis correction, requiring new management approaches.”

Reference

  1. Cooke EJ, vonDrygalski A, Wyseure T, et al. Vascular remodelling associated with hemophilic joint bleeding occurs independently of hemostasis correction and promotes vascular permeability and re-bleeding [Abstract M-FPMED02-007 (856)]. Haemophilia. 2018;24(suppl. 5):213-214.

Related Resources

You must be a registered member of Cancer Therapy Advisor to post a comment.

Sign Up for Free e-newsletters



Regimen and Drug Listings

GET FULL LISTINGS OF TREATMENT Regimens and Drug INFORMATION

Bone Cancer Regimens Drugs
Brain Cancer Regimens Drugs
Breast Cancer Regimens Drugs
Endocrine Cancer Regimens Drugs
Gastrointestinal Cancer Regimens Drugs
Gynecologic Cancer Regimens Drugs
Head and Neck Cancer Regimens Drugs
Hematologic Cancer Regimens Drugs
Lung Cancer Regimens Drugs
Other Cancers Regimens
Prostate Cancer Regimens Drugs
Rare Cancers Regimens
Renal Cell Carcinoma Regimens Drugs
Skin Cancer Regimens Drugs
Urologic Cancers Regimens Drugs